KR101839846B1 - In vivo implantable drug pump driven by external magnetic field - Google Patents

Abstract

The bioactive liquid pump capable of operating with an external magnetic field includes a micro body including a chemical liquid chamber and an intermediate discharge port, a membrane covering one side of the chemical liquid chamber opposite to the intermediate discharge port, a membrane covering the outer surface of the micro- And a magnetic driving part formed on the membrane, wherein the magnetic driving part moves in one direction within the magnetic field, and the membrane presses a part of the chemical solution in the chemical liquid chamber to the intermediate discharge port , The drug solution can be discharged through the drug solution outlet while the resistance valve is partially deformed.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to an in vivo chemical pump capable of operating with an external magnetic field,

TECHNICAL FIELD The present invention relates to a bioactive liquid pump that can be implanted in a living body and can be supplied in vivo periodically or externally.

It is known that AMD, retinal vein occlusion (RVO), diabetic macular edema (DME), and posterior uveitis are typical retinal degenerations. Mechanism is mainly caused by retinal microangiopathy. -VEGF agents or steroid agents in intravitreal bolus injection.

However, existing therapies that directly injected into the vitreous cavity are ineffective as a result of vascular outflow or are caused by cataract / glaucoma side effects (retinal detachment, acute visual loss, corneal erosion, subconjunctival hemorrhage) It is necessary to develop long-term on-demand drug delivery through an intravitreal implantable drug delivery structure with a high-efficiency, high-precision targeting treatment effect on the nano-micro range.

In this regard, WO 2003/077972 relates to an "implantable drug delivery system ", wherein the implantable drug delivery device comprises a core body, wherein the core body comprises a single bay wire or a plurality of small bays Lines, and each bay line is covered with a screen. The implantable drug delivery device is located within the animal's body and the drug diffuses through the holes in the screen to provide treatment for the disease or condition.

Korean Patent Publication No. 2010-0073431 discloses a capsule type dosing device and a method of administering the same, wherein the capsule type dosing device includes a medicine holding part and a circuit holding part, a blocking wall is provided therebetween, Wherein the circuit holding part includes a power supply part, a communication part for receiving a medicine emission signal from the outside, and a control part for controlling the medicine discharge, and a medicine discharge port for discharging medicine is formed in the medicine holding part, And a hydrogen generating film laminated on the heating part and the heating part is formed on the first surface.

The present invention provides a chemical liquid pump which is implanted at a specific position in a living body and can control nanocomposite-drug release when necessary.

The present invention provides a bioactive liquid chemical pump capable of not only releasing a drug once in a living body but also continuously releasing the drug while staying in the living body twice or more if necessary.

The present invention provides a bioactive liquid chemical pump having a structure capable of decomposing in vivo after releasing a drug while staying in the living body for months or years.

The present invention provides a drug solution pump as a drug delivery body capable of implanting VEGF (neovascular receptor) target-nanocomposite into a glass body cavity and supplying a drug when necessary.

According to an exemplary embodiment of the present invention for achieving the objects of the present invention described above, a bioactive liquid pump operable with an external magnetic field includes a micro body including a chemical liquid chamber and an intermediate discharge port, A resistance valve plate covering the outer surface of the micro body and covering the outer surface of the intermediate body so as to cover the outer surface of the micro body and formed at a position spaced apart from the intermediate discharge port and a magnetic drive part formed on the membrane, The membrane can press some of the chemical liquid in the chemical liquid chamber to the intermediate discharge port and the chemical liquid can be discharged through the chemical liquid discharge port while partially deforming the resistance valve film.

In order to easily deform the resistance valve film by pressing the membrane, a non-adhesion region can be formed between the resistance valve film and the outer surface of the micro body. For example, a micro body and a resistance plate can be formed using PDMS or the like. In order to prevent them from being intertwined with each other, a resistance plate and a micro body can be treated with plasma to form an adhesion region and a non-adhesion region.

In addition, a plurality of grooves may be formed on the outer surface of the micro-body in contact with the resistance plate film to form a non-adhesive region. For example, a plurality of grooves can be formed in the micro-body by laser cutting or the like, and a plurality of grooves can be formed in the micro-body to prevent the chemical liquid from leaking between the intermediate discharge port and the chemical-liquid outlet.

The chemical liquid pump of the present invention can be implanted at various positions in the living body. For example, when the chemical pump of the present invention is transplanted into the vitreous cavity, treatment of retinal degenerative diseases (wet AMD, retinal vein occlusion (RVO), diabetic macular edema (DME), and posterior uveitis) Can be discharged periodically or by external stimulation, and a certain amount can be discharged over a short period or a long period.

In addition, it is possible to provide a change in the amount of movement by the magnetic driving part according to the intensity of the magnetic field, and to control the amount of discharge, the number of times of discharge, and the discharge period by adjusting the magnetic field.

The biodegradable drug solution pump of the present invention is implanted at a specific position in a living body and can control nanocomposite drug release if necessary. The bioactive drug solution pump can be used not only for one-time release of drug in vivo, The drug can be released continuously.

For example, when implanted in the vitreous cavity, it is possible to supply drugs necessary for the treatment of retinopathy, which is a posterior ophthalmic disease, and when it is supplied by repeated injections in the glass body cavity as in the conventional case, the retinal detachment, acute visual loss, Serious side effects such as hemorrhage may occur. In the case of the bioactive drug liquid pump of the present invention, the drug solution can be delivered to and supplied to the target in an amount required for on-demand treatment.

The body of the chemical pump is a DDS structure that can be biodegraded without rehearsal or surgically removes the structure with the chemical solution exhausted in the case of the organ type and can be adjusted to the appropriate timing and amount as the physiological condition of the patient changes have.

In addition, it is possible to prevent the toxicity of surrounding tissues from being caused by excessive drug injection, and conversely, if necessary, the dosage can be increased to deliver drugs with a high dose, thereby maximizing the therapeutic effect.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a view for explaining the use of a bioactive liquid chemical pump according to an embodiment of the present invention; FIG.
FIG. 2 is a view for explaining the structure of the bioactive liquid chemical pump of FIG. 1; FIG.
FIG. 3 is a view for explaining the operating state of the bioactive liquid chemical pump of FIG. 2. FIG.
4 is a view for explaining the operation principle of the bioactive liquid chemical pump according to the embodiment of the present invention.
5 is a view for explaining a cross-sectional structure of a bio-chemical liquid pump according to an embodiment of the present invention.
6 to 8 are views for explaining a manufacturing process of the bio-chemical liquid pump according to an embodiment of the present invention.
9 is a view for explaining the bonding process of the resistance plate and the intermediate partition according to an embodiment of the present invention.
10 is a plan view of a chemical pump according to an embodiment of the present invention.
11 is a side view of the chemical liquid pump of FIG.
FIGS. 12 and 13 are views for explaining the process of discharging the chemical liquid when the chemical liquid pump shown in FIG. 10 is actually exposed to a magnetic field.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments. For reference, the same numbers in this description refer to substantially the same elements, and the contents described in the other drawings under the above-mentioned rules can be explained by quoting, and the contents which are judged to be obvious to the person skilled in the art or repeated can be omitted.

FIG. 1 is a view for explaining an example of use of a bioactive liquid chemical pump according to an embodiment of the present invention, FIG. 2 is a view for explaining a structure of a bioactive liquid chemical pump of FIG. 1, Fig. 8 is a view for explaining the operating state of the edible liquid chemical pump. Fig.

Referring to FIG. 1, the bioactive liquid pump 100 according to the present embodiment may be inserted into the glass body 10. A single operation is required to be inserted into the glass body cavity 10 and can be fixed to one side within the glass body cavity 10.

Depending on the material of the bioactive food liquid pump 100, it may be formed of a material such as polyester or polyurethane and may be biodegraded in vivo. However, in some cases, it is a material which is not biodegradable In this case, a separate operation may be added to remove the chemical liquid pump 100.

2, the biochemical liquid medium pump 100 includes a micro body 110 including a chemical liquid chamber 112 and an intermediate discharge port 114, a pair of side surfaces of the chemical liquid chamber 112 opposed to the intermediate discharge port 114, A resistance valve film 130 covering the outer surface of the micro-body 110 so as to cover the covering membrane 120 and the middle outlet 114 and having a chemical-solution outlet 134 formed at a position spaced apart from the intermediate outlet 114, and And a magnetic driving unit 140 formed on the membrane 120.

The chemical liquid pump 100 may be formed using a PDMS, a hydrogel structure, a silicone polymer, or the like, and may be formed through a soft lithography process or the like. It can be formed using a biodegradable or non-biodegradable material depending on the period of time which is harmless in vivo and must be maintained in vivo.

The micro-body 110 and the membrane 120 may form the chemical liquid chamber 112. The chemical liquid 20 may be stored in the chemical liquid chamber 112 while the chemical liquid pump 100 operates and the stored chemical liquid 20 may be discharged through the intermediate discharge port 114 formed at one side of the micro body 110 .

In this embodiment, the membrane 120 and the intermediate outlet 114 are formed in opposite directions to each other, but in some cases, they may be formed in directions intersecting each other, and the action of the membrane may be such that the physical If they form a relationship, they can be seen as facing each other.

The resistance plate 130 may be formed on the outer wall of the micro body 110 where the intermediate discharge port 114 is formed. The resistance plate 130 may be relatively thin compared to the layer of the micro body 110 and deformed earlier than the micro body 110 by the operation of the membrane 120.

The resistance plate 130 and the micro body 110 are adhered to each other around the middle outlet 114 so as to seal each other and form a non-adhesive area around the middle outlet 114, And a drug solution outlet 134 may be formed on one side of the region where the drug solution can be deformed. The chemical solution discharge port 134 may be spaced apart from the intermediate discharge port 114 and may control the discharge amount of the chemical solution discharged once according to the size of the chemical solution discharge port 134, the spaced distance, have.

A magnetic driving part 140 may be integrally coupled to the membrane 120. In this embodiment, the magnetic driver 140 may be formed by mixing PDMS and magnetic nanoparticles, and may move in one direction within the magnetic field.

3, when the chemical liquid pump 100 is positioned within the magnetic field, the magnetic drive unit 140 and the membrane 120 can be moved toward the intermediate discharge port 114. As shown in FIG. The drug solution 20 in the chemical solution chamber 112 can be moved between the micro body 110 and the resistance film 130 through the intermediate discharge port 114 by the moved membrane 120 and the resistance film 130 can be partially A part of the chemical liquid can be discharged to the outside of the chemical liquid pump 100 through the chemical liquid discharge port 134 while expanding.

4 is a view for explaining the operation principle of the bioactive liquid chemical pump according to the embodiment of the present invention.

Referring to FIG. 4B, since the resistance valve 130 limits the movement of the chemical liquid between the intermediate discharge port 114 and the chemical liquid discharge port 134 while the chemical liquid pump 100 is not operated, And the resistance plate 130 is attached to the outer wall of the micro body 110, so that foreign substances can be prevented from flowing into the chemical liquid chamber 112 or leakage of the chemical liquid in the chamber to the outside.

Then, as shown in (a), when the magnetic field is applied, the partial pressure of the resistance plate film 130 is increased by the operation of the membrane 120, and the intermediate discharge port 114 and the chemical liquid discharge port 134 are opened, Can be discharged.

5 is a view for explaining a cross-sectional structure of a bio-chemical liquid pump according to an embodiment of the present invention.

5, the biochemical liquid pump 200 includes a micro body 210, a membrane 220, a resistance plate 230, and a magnetic driving unit 240.

The microbody 210 and the membrane 220 form a chemical liquid chamber 212. The stored chemical liquid 20 is discharged to the outside through the intermediate discharge port 214 by the operation of the membrane 220 and the magnetic driving part 240 .

The resistance plate 230 is formed on the outer wall of the micro body 210 in which the intermediate discharge port 214 is formed and the magnetic drive unit 240 is integrally coupled to the membrane 220, .

In this embodiment, a non-adhesive region 260 is formed between the resistance plate 230 and the micro-body 210, and a plurality of grooves 260 are formed on the outer surface of the micro- (216) may be formed. The plurality of grooves 216 may be formed in the form of a lattice with a depth of about 25 탆 on the outer surface of the micro body 210 to smoothly operate the resistance plate 230. Through the patterning, 230 are adhered to the outer surface of the micro-body 210 can be solved. Also, the resistance film 230 and the membrane 220 can also increase the driving displacement of both membranes by using a PDMS membrane having a thickness of about 25 占 퐉.

6 to 8 are views for explaining a manufacturing process of the bio-chemical liquid pump according to an embodiment of the present invention.

In general, the chemical liquid pump according to the present embodiment can be manufactured based on a soft lithography process. The chemical liquid pump according to the present embodiment can be manufactured through a magnetic composite polymer (MCP) membrane in which a magnetic nanoparticle is combined with a flexible PDMS material, And the bioactive liquid pump can be manufactured by using the magnetic drive unit.

The first part including the membrane 220 and the magnetic driving part 240 is fabricated to fabricate the chemical pump made of the PDMS material and the second part of the micro body 210 and the resistance film 230 (FIG. 7), the first part and the second part are assembled, the drug is injected into the pump through a microchannel using a syringe and a microneedle, and a microchannel is formed by PDMS So that the chemical liquid pump 200 can be completed (FIG. 8).

Referring to FIG. 6, a PDMS (polydimethylsiloxane) layer 320 for a membrane 220 is coated on the substrate by spin coating, and a magnetic-PDMS layer (not shown) for the magnetic driver 240 is formed on another substrate 340) can be spin-coated and punched according to the pattern (b). Silane-treated silica can be used as the substrate in this embodiment. The magnetic-PDMS layer 340 can be formed by using EMG1200 magnetic nanoparticles manufactured by ferrotec and Sylgard 184 PDMS in a ratio of 1: 1 Can be mixed and manufactured.

The first part can be manufactured by bonding a magnetic driving part 240 punched on the PDMS layer 320 and forming a bottom part 250 that forms a PDMA space around the magnetic driving part 240.

7, a pattern mold 316 corresponding to a plurality of grooves 216 is formed in a grid pattern on a substrate and an intermediate partition wall 312 for forming the micro body 210 is formed using PDMS (F). The intermediate partition wall 312 can be separated from the substrate and the pattern mold 316 and then placed on a substrate or a jig to form an intermediate discharge port 214 by laser cutting g. The resistive film 230 can be formed on the PDMS film 312 having a thickness of about 25 占 퐉 (h). The resistance judgment () may further include a chemical liquid discharge port 234 formed at a position horizontally spaced apart from the intermediate discharge port 214.

Here, the non-adhesive region 260 may be formed between the resistance plate 230 and the intermediate partition 312, and between the resistance plate 230 and the intermediate partition 312, around the intermediate outlet 214. The drug solution can be moved to the non-adhering region 260 and discharged through the drug solution outlet 234. [

A side wall 314 for forming a chemical liquid chamber can be formed around the intermediate partition 312 after the intermediate partition 312 and the resistance plate 230 are bonded to each other. The microchannel 316 can be further formed.

Referring to FIG. 8, the chemical liquid pump may be assembled by bonding the first part of FIG. 6 and the second part of FIG. By bonding the second part to the upper part of the membrane 220, the chemical liquid chamber 212 is formed, and microchannels 316 are formed on the side thereof (j).

Then, the chemical liquid can be injected into the chemical liquid chamber using a syringe (k), and the microchannel 210 can be completed by sealing the microchannel 316 with the PDMS to seal the chamber into which the chemical liquid is injected l).

9 is a view for explaining the bonding process of the resistance plate and the intermediate partition according to an embodiment of the present invention.

Referring to FIG. 9, a mask using PDMS may be deposited on the intermediate partition wall 412 having an intermediate discharge port corresponding to the non-adhered area and treated with O ₂ plasma. Also, a mask using PDMS may be stacked on the resistance plate 430 on which the medicament solution outlet is formed, corresponding to the non-adhesion area, and this can also be treated with O ₂ plasma.

Thus, in the process of bonding the intermediate partition wall 412 and the resistance plate 430, a non-adhesion area 460 can be formed around the middle outlet, and the resistance plate (430) 430 can be smoothly operated as a kind of valve.

FIG. 10 is a plan view of a chemical pump according to an embodiment of the present invention, FIG. 11 is a side view of the chemical pump of FIG. 10, and FIGS. 12 and 13 are cross- FIG. 3 is a view for explaining a process of discharging a chemical liquid when actually exposed to a magnetic field.

10 and 11, a resistance valve, a micro body formed with a chemical liquid chamber, a PDMS membrane, and a magnetic driving part are formed from above, and the middle outlet and the chemical solution outlet are formed at a spaced- The lattice pattern grooves are formed on the outer surface of the resistance plate and the interconnection between the resistance plate and the micro body can be prevented.

12 and 13, the chemical solution remains in the chamber without being exposed to a magnetic field, and is not discharged. However, when the external magnetic field is applied at about 100 to 200 mT, the chemical solution is discharged from the chemical solution outlet of the resistance valve (B), a certain amount is discharged from the drug solution outlet (c), and it is diffused to the periphery ((d) to (f)).

This process may be performed by applying an external magnetic field for one to two months or at a constant cycle to discharge the chemical solution, and a magnetic field may be applied once or twice to eject a desired fixed amount.

In the case of Lucentis or Isillis, a macular degenerative agent used mainly in Korea, it should be injected once a month into the vitreous cavity, resulting in serious side effects such as retinal detachment, acute visual loss, corneal erosion and subconjunctival hemorrhage In the case of the chemical liquid pump according to the present embodiment, as an implantable transporter, there is an advantage that a drug can be delivered without any pain for a long period of time, such as one year or two years, with minimal drug delivery at a desired time.

Although the present invention has been described with reference to the preferred embodiments thereof, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention as defined in the following claims. It can be understood that

100: Biochemical liquid pump 110: Micro-body
112: chemical liquid chamber 114: intermediate discharge port
120: membrane 130: resistance valve
134: chemical solution outlet 140: magnetic drive part

Claims (5)

A micro-body including a chemical liquid chamber and an intermediate outlet;
A membrane that covers one side of the chemical liquid chamber opposite to the intermediate discharge port;
A resistance valve plate covering the outer surface of the micro body to cover the intermediate discharge port and including a chemical liquid discharge port formed at a position spaced apart from the intermediate discharge port; And
And a magnetic driving part formed on the membrane,
Wherein the membrane drives the part of the chemical solution in the chemical solution chamber to the intermediate discharge port while the magnetic drive part moves in one direction within the magnetic field and the resistance valve film partially deforms to discharge the chemical solution through the chemical solution outlet Pump. The method according to claim 1,
Wherein the partition of the micro-body on which the intermediate discharge port is formed is thicker than the thickness of the resistance plate. The method of claim 1,
And a non-adhesive region is formed between the resistance plate and the outer surface of the micro-body. 4. The method of claim 3,
Wherein a plurality of grooves are formed on an outer surface of the micro-body in contact with the resistance plate to form the non-sticking region, thereby restricting adhesion of the resistance plate to the outer surface of the micro-body. The method according to claim 1,
Wherein the magnetic drive part is formed by mixing magnetic particles in a hydrogel material.

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